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Flashcards

T Cell Activation

Caitlin M BM325 3 English 38 cards

Cards in this deck (38)

  1. 1What are the stages of T cell activation?1. Presentation and subsequent recognition of specific anitgen
    2. Activation/early phase initiation of signal transduction cascade (membrane)
    3. Activation/intermediate phase initiation of signal transduction cascade (into the cell)
    4. Activation/late phase initiation of gene transcription/nuclear events
    5. Functional responses effector-cell end-actions
  2. 2How did Gell and Benacerraf prove differences in antigen recognition?It was shown that denatured (boiled protein, usually ovalbumin) antigen can still activate T cells but not B cells
    Indicates that T cells do not require an antigen to be in its tertiary structure
  3. 3What is denaturation of a protein?Changes the shape of the protein by collapsing the hydrogen bonds and the 3D shape
    It is not broken down
  4. 4Question TextAnswer Text
  5. 5What is the definition of fixed?Metabolically killed by gamma radiation or formaldehyde but structurally intact
  6. 6What are the two antigen processing pathways?Cytosolic pathway
    Endocytic pathways
  7. 7What is the cytosolic pathway?Endogenous proteins
    Makes peptides for MHC class I
    CD8/cytotoxic T cells
  8. 8What is the endocytic pathway?Exogenous proteins
    Peptides for MHC class II
    CD4/T helper cells
  9. 9describe the cytosolic pathway (MHC I)Processes an antigen to yield the antigen on MHC class I molecules
    Job is to remodel proteins regardless of what they are/where they came from
  10. 10What are the steps in the cytosolic pathway?A protein in the cytosol, not necessarily from an antigen/pathogen
    Proteasomes chop the proteins into random fragments of 8-20 peptides
    TAP takes peptide fragments to the ER where there is a preformed MHC class I molecule
    These peptides are placed onto a MHC molecule
    The MHC class I molecule is packaged and transported to the Golgi
  11. 11How do T cells proliferate?Clonal expansion
  12. 12What are the steps in the endocytic pathway?An endosome containing protein fuses with a lysosome
    The natural process of chopping up the protein by proteolytic enzymes within the lysosome occurs
    The lysosome compartment then fuses with the golgi which has a premade MHC class II molecule inside it
    CLIP blocks the MHC II
    CLIP is cleavedoff which allows the protein fragments to be loaded onto the MHC II molecule
  13. 13Describe the endocytic pathwayProcessing of an antigen via the vesicle pathway to yield antigen on MHC class II molecule
  14. 14What are the parts of an MHC Class I molecule?Peptide Binding Cleft
    Membrane distal Domains (alpha 1 and 2)
    Membrane proximal domains (Ig fold structure)
    B2 microglobuliin
    CD8
    Transmembrane segment
    Cytoplasmic tail
  15. 15What are the parts of an MHC class II molecule?Peptide binding cleft
    Membrane distal domains
    Alpha 1 and alpha 2
    CD4
    Membrane proximal domains
    Transmembrane segment
    Cytoplasmic tails
  16. 16Describe the peptide binding cleft of a MHC class IPeptide 8-10 amino acids long
  17. 17Describe the peptide binding cleft of MHC class IIPeptide 15-20 amino acids long, full length of cleft, can hang out the side
  18. 18What are the parts of the TCR?4 immunoglobulin domains
    Constant and variable regions
    alpha chain and beta chain
    Disulphide bonds
    Transmembrane segments
    Cytoplasmic tails
  19. 19What is the TCR?T cell receptor which does the recognition and binding it loops like an antibody; it has alpha and beta chains; constant and variable regions
    On each T cell the combination is identical, but the combination of amino acids in the variable domain are different
    TCR only recognises, it is not a signalling molecule
  20. 20What are the TCR components?Alpha chain
    Beta chain
    2 Homodimers
    CD3 complex
    CD4
    Lck
    CD45
  21. 21What are the alpha and beta chains?The TCR
  22. 22What is the CD3 complex?Has four chains and is a cell surface marker for T cells
  23. 23What is CD4?Receptor for MHC class II molecules
  24. 24What is lck?A kinase with signalling ability which always associates with CD4; allows lck to access the other proteins
  25. 25What s CD45?A phosphotase
  26. 26What is the significance of CD4?MHC II molecule taken to the CD4 which takes the antigen close to the TCR allowing the T cell to test the antigen; also allows clustering
  27. 27What are SH2/SH3?Src homology regions 2/3
    SH2: 100 amino acids/Tyr-P docking
    SH3: 60 amino acids, proline rich targets
  28. 28What is an ITAM?Immunoreceptor Tyrosine Activation Motifs
    Phosphorylated ITAMs are docking sites for kinases
  29. 29What are the properties of lck kinase?Fatty acids link it to the membrane
    Lipid soluble
    Inactive when not phosphorylated
  30. 30Describe the tyrosine phosphorylation sequence/signal transductionSignalling following binding of antigen by TCR and the recruitment of lck to the TCR complex when CD4 binds to MHC II on the APC
    ITAMs become phosphorylated and subsequently PLC is recruited, activated and hydrolyses PIP2 to yield IP3 and DAG to activate 2 pathways
    CD3 are phosphorylated the homodimers are phosphorylated to allow ZAP-70 to dock
    PLC generates molecules that are soluble and penetrate into the cell
    It takes membrane phospholipids (PIP2) and cleaves it into DAG and IP3
    IP3's role is to release calcium; zap-70 is an adaptor protein that allows other proteins to stick to it and create a scaffold DAG is an activator of PKC
  31. 31Explain calcium signals in activated T cellsActivation of calcium release in t cells via the TCR by directly ligating TCR molecules (not requiring antigen) an allowing membrane components to be brought together by using an anti-TCR antibody
    This experiment shows directly the increase in intracellular calcium using calcium sensitive dyes
  32. 32What are the three major signal activation pathways?Calcium pathway
    PKC pathway
    Ras/Rac-GTP pathway
  33. 33Describe the calcium pathwayCalcium binds to calmodulin to activate the enzyme calcineurin
    Calcineurin removes the phosphate from NFATc
    NFATc remains cytosolic when it has a phosphate attached
    NFATc translocates from the cytoplasm to the nucleus
    NFATn is a transcription factor for regulating DNA which codes for mRNA
  34. 34Describe the PKC pathwayPKC phosphorylyses the NFkb kinase which causes it to disengage from the Ik-b to allow it to enter the nucleus
    Nf-kb is a transcription factor
  35. 35Describe the Ras/Rac-GTP pathwayRas/Rac-GTP activates MAP-k and JNK
    MAP-k activates the transcription factor fos and JNK activates the transcription factor jun
    Jun and fos are called AP-1
  36. 36Describe the gene transcription phase1. Immediate genes eg fos-c,c-myc
    2. Early genes eg IL-2, IL-2Ra, cytokines (within 2-12 hours)
    3. Late genes eg MHC, adhesion molecules, VLA (up to a week)
  37. 37What is CD28's role?One of the proteins on the surface of T cells
    it interacts with B7 ligands on antigen surfaces to produce co-stimulation signals
    Optimal activation requires its binding
  38. 38What is the role of CTLA-4?A transmembrane protein expressed on CD4 and CD8 t cells
    It blocks T cell proliferation by telling the cell to undergo apoptosis

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3 BM325 Flashcards on T Cell Activation, created by Caitlin M on 17/11/2017.
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Caitlin M
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